Chronic HCV :

Epidemiology and

Natural History

*95% Confidence Interval

Hepatitis C Virus Infection
United States

New infections (cases)/year 1985-89 242,000

1998 40,000

Deaths from acute liver failure Rare

Persons ever infected (1.8%) 3.9 million (3.1-4.8)*

Persons with chronic infection 2.7 million (2.4-3.0)*

Of chronic liver disease - HCV-related 40% - 60%

Deaths from chronic disease / year

8,000-10,000

Adapted from CDC Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/
Accessed 01/18/03.

Estimated Incidence of Acute
HCV Infection United States,
1960-1999

Decline in

transfusion recipients

Decline in injection

drug users

Adapted from CDC Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset

/

Accessed

01/18/03
Hepatology 1200;31:777-82; Hepatology 1997;26:62S-65S

*Adapted from Brown RS. Epidemiology and Natural History of Hepatitis C. Presented
at an ACG Clinical Implications meeting April 6, 2000 in Dallas, TX. Source: CDC
Sentinel Counties Study of Acute Viral Hepatitis

Anti-HCV test

(1st

generation)

licensed

Anti-HCV test

(2nd

generation)

licensed

Decline among

injecting drug users

Decline among

transfusion

recipients

198

3

198

5

198

7

198

9

199

1

199

3

Year

Acute

HCV

Liver Disease

from HCV

Incidence of HCV:

Infection vs Disease

*

Surrogate

testing

of blood donors

Hepatitis C Epidemiology

Burden of Disease

 Though incidence is falling, disease burden is
increasing due to prior peaks

 Variable course, many patients will die of other causes

 However, cirrhosis, hepatic failure, and liver cancer will
occur over time in many HCV patients

 HCV is the leading indication for liver transplantation

 Predicting who will develop complications of liver disease
is the challenge of hepatology in the coming years

*Adapted from Brown RS. Epidemiology and Natural History of Hepatitis C.
Presented at an ACG Clinical Implications meeting April 6, 2000 in Dallas, TX.

Future Prevalence of HCV

0

1.0

2.0

3.0

4.0

1960 1970 1980 1990 1200 2010 2020 2030

Years

Years

P

re

v

a

le

n

c

e

o

f

H

C

V

I

n

fe

c

ti

o

n

Percent

Armstrong GL, Alter MJ, McQuillan GM, Margolis HS. The past incidence of hepatitis C virus
infection:
Implications for the future burden of chronic liver disease in the United States.
Hepatology. 1200;31:777-782.

Individuals infected at any

Individuals infected at any

time

time

Individuals infected for > 20

Individuals infected for > 20

years

years

Prevalence of HCV Infection
United States, 1988-1994

13

0.5 (0.3-1.0)

2.9

Other

7

0.3 (0.2-0.3)

2.1

Mex

American

20

0.8 (0.6-1.0)

3.2

Black

61

2.4 (1.8-3.1)

1.5

White

100

3.9 (3.1-4.8)

1.8

Total

Percent

of

Infections

Est. Infections

Millions

(95% CI)

Percent

Anti-

HCV

Positive

Group

Adapted from CDC Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Prevalence of HCV Infection

by Age and Gender, United
States

,

1988-1994

CDC, NHANES IIIAdapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Males

Females

Total

Estimated Prevalence of HCV
Infection

at Age 60, by Year of Birth

Birth year of cohort

P

re

v

a

le

n

c

e

a

t

a

g

e

6

0

Armstrong GL et al. Hepatology 2000;31:777-782.

Transmission of HCV

 Percutaneous

 Injecting drug use
 Clotting factors before viral inactivation
 Transfusion, transplant from infected donor
 Therapeutic (contaminated equipment, unsafe injection

practices)

 Occupational (needlestick)

 Permucosal

 Perinatal
 Sexual

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset..Accessed 01/18/03.

Source: CDC Sentinel Counties

Reported Cases of Acute

Hepatitis C

by Selected Risk Factors, United

States,1983-1998*

Injecting drug use

Sexual

Health related work

Transfusion

* 1983-1990 based on non-A, non-B hepatitis

CDC Sentinel Counties Study
Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset.
Accessed 01/18/03.

Sources of Infection for

Hepatitis C

(<

1990’s

)

Sexual 15%

Other * 5%

Unknown 10%

Injecting drug use 60%

Transfusion 10%

(before screening)

*Nosocomial; Health-care work; Perinatal

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/ Accessed
01/18/03.

Sources of Infection for
Hepatitis C (1995-2000)

Sexual 18%

Other * 5%

Unknown 9%

Injecting drug use 68%

*Nosocomial; Health-care work; Perinatal

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.
Alter MJ. Hepatology 2002;36:S93-S98.

1.7 (1.2-2.3)
1.4 (0.9-2.4)

Occupational blood exposure
Lived with hepatitis case

2.7 (1.7-4.2)

Pierced ears/body parts

3.2 (1.9-5.4)

Needlestick, bloody

3.9 (2.5-6.1)

Tattoo

5.0 (2.6-9.8)

In jail more than 3 days

9.7(5.8-16.2)

Sex with IDU

8.3 (5.5-12.4)

Blood transfusion; Non-IDU

134 (68-268)

IDU

OR (95% CI)*

Variable (adjusted for IDU)

Independent Risk Factors for
HCV

Seropositivity Among US Blood Donors,
1994-1995

*Adjusted for education, alcohol intake, and sex with someone with hepatitis.
Murphy EL et al. Hepatology 2000; 31:756-762

Injecting Drug Use and
HCV Transmission

 Highly efficient among injection drug users

 Rapidly acquired after initiation

 Four times more common than HIV

 Prevalence 60-90% after 5 years

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Posttransfusion Hepatitis C

All volunteer donors

HBsAg

Donor Screening for HIV Risk Factors

Anti-HIV

ALT/Anti-HBc

Anti-HCV

Improved

HCV Tests

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Nosocomial Transmission of

HCV

 Recognized primarily in context of

outbreaks

 Contaminated equipment

 Hemodialysis*
 Endoscopy

 Unsafe injection practices

 Plasmapheresis*, phlebotomy
 Multiple dose medication vials
 Therapeutic injections

*Reported in US
Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Occupational Transmission of

HCV

 Inefficiently transmitted by occupational exposures

 Average incidence 1.8% following needle stick from
HCV-positive source

 Associated with hollow-bore needles

 Case reports of transmission from blood splash to eye

 No reports of transmission from skin exposures to blood

 Prevalence 1-2% among health care workers

 Lower than adults in the general population
 10 times lower than for HBV infection

 Presence of recognized risk factor does not necessarily

equate with “increased risk”

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset.
Accessed 01/18/03.

HCW to Patient Transmission of
HCV

 Rare

 In U.S., none related to performing invasive procedures

 Most appear related to HCW substance abuse

 Reuse of needles or sharing narcotics used for self-

injection

 Reported mechanism for transmission of other

bloodborne pathogens from some HCWs

 No restrictions routinely recommended for
HCV-infected HCWs

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset.
Accessed 01/18/03.

Perinatal Transmission of
HCV

 Transmission only from women HCV-RNA

positive at delivery

 Average rate of infection 6%
 Higher (17%) if woman co-infected with HIV
 Role of viral titer unclear

 No association with

 Delivery method
 Breastfeeding

 Infected infants do well

 Severe hepatitis is rare

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Sexual Transmission of HCV

 Case-control, cross sectional studies

 Infected partner, multiple partners, early sex, non-use
of condoms, other STDs, sex with trauma
 MSM no higher risk than heterosexuals

 Partner studies

 Low prevalence (1.5%) among long-term partners

 infections might be due to common percutaneous

exposures (e.g., unsafe injections, drug use)

 Male to female transmission more efficient

 more indicative of sexual transmission

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.00

Sexual Transmission of HCV

 Occurs, but efficiency is low

 Rare between long-term steady partners
 Factors that facilitate transmission between partners

unknown (e.g., viral titer)

 Accounts for 15-20% of acute and

chronic infections in the United States

 Sex is a common behavior
 Large chronic reservoir provides multiple

opportunities for exposure to potentially infectious

partners

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03,

Household Transmission of
HCV

 Rare but not absent
 Could occur through

percutaneous/mucosal exposures to blood

 Theoretically through sharing of contaminated

personal articles (razors, toothbrushes)

 Contaminated equipment used for home

therapies

 Injections*
 Folk remedies

*Reported in US
Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Other Potential Exposures to

Blood

 No or insufficient data showing

increased risk

 Intranasal cocaine use, tattooing, body piercing,
acupuncture, military service

 Limited number of studies showing

associations that cannot be generalized

 Convenience or highly selected groups (mostly blood

donors)

 No associations in acute case-control or

population-based studies

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Case-Control Studies of

Acute Hepatitis C,

U.S. Exposures Not Associated with Acquiring Disease,

1979-1985

4.9

1.3

Military Service

2.5

4.1

Foreign Travel

1.0

0

Acupuncture

0.5

0.7

Tattooing

3.0

2.7

Ear Piercing

5.0

4.1

Health Care Work (No Blood
Contact)

23.5

24.3

Dental Work

29.5

30.4

Medical Care Procedures

Controls (%)

n=200

Cases (%)

n=148

Exposure (prior 6 months)

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03
Source: JID 1982;145:886-93; JAMA 1989;262:1201-5.

Other Potential Exposures to

Blood

 Biologically plausible but no data showing these

practices, procedures, or histories alone place

persons at increased risk for HCV

 May be limited to certain settings and account

for small fraction of cases

 e.g., prisons, unregulated practitioners, populations

with certain cultural practices, etc.

 Risk factor or high prevalence identified in

selected subgroup cannot be extrapolated to the

population

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Reduce or Eliminate Risks for

Acquiring HCV Infection

 Screen and test donors
 Virus inactivation of plasma-derived

products

 Risk-reduction counseling and services

 Obtain history of high-risk drug and sex behaviors
 Provide information on minimizing risky behavior,

including referral to other services

 Vaccinate against hepatitis A and/or hepatitis B

 Infection control practices

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slidese. Accessed
01/18/03.
MMWR 1998;47 (No. RR-19)

Reduce Risks for Disease

Progression

and Further Transmission

 Identify persons at risk for HCV and test

to determine infection status

 Routinely identify at risk persons

through history, record review

 Provide HCV-positive persons

 Medical evaluation and management

 Counseling

 Prevent further harm to liver
 Prevent transmission to others

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.
MMWR 1998;47 (No. RR-19)

HCV Prevalence by Selected

Groups

United States

Hemophilia

Injecting drug users

Surgeons, PSWs

Hemodialysis

Average Percent Anti-HCV Positive

Gen population adults

Military personnel

STD clients

Pregnant women

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

HCV Testing Routinely

Recommended

Based on increased risk for infection

 Ever injected illegal drugs
 Received clotting factors made before 1987
 Received blood/organs before July 1992
 Ever on chronic hemodialysis
 Evidence of liver disease

Based on need for exposure management

 Healthcare, emergency, public safety workers after

needle stick/mucosal exposures to HCV-positive blood

 Children born to HCV-positive women

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Postexposure Management

for HCV

 IG, antivirals not recommended for prophylaxis
 Follow-up after needlesticks, sharps, or mucosal

exposures to HCV-positive blood

 Test source for anti-HCV

 Test worker if source anti-HCV positive

 Anti-HCV and ALT at baseline and 4-6 months later

 For earlier diagnosis, HCV RNA by PCR at 4-6 weeks

 Confirm all anti-HCV results with RIBA

 Refer infected worker to specialist for medical

evaluation and management

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Routine HCV Testing

Not Recommended

(Unless Risk Factor

Identified)

 Health-care, emergency medical,

and public safety workers
 Pregnant women
 Household (non-sexual) contacts of

HCV-positive persons

 General population

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Routine HCV Testing
of Uncertain Need

 Not confirmed as risk factor/prevalence

unknown

 Recipients of transplanted tissue
 Intranasal cocaine or other non-injecting illegal drug users
 History of tattooing, body piercing

 Confirmed risk factor but prevalence of

infection low

 History of STDs or multiple sex partners

 Long-term steady sex partners of HCV-positive persons

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

STOP

HCV Infection Testing

Algorithm

for Diagnosis of Asymptomatic

Persons

EIA for Anti-HCV

Negative

(non-reactive)

Positive (repeat
reactive)

OR

RIBA for Anti-HCV

RT-PCR for HCV RNA

Negativ

e

Additional Laboratory

Evaluation (e.g. PCR, ALT)

Negative

Positive

Indetermin
ate

Medical

Evaluation

Positiv
e

Negative PCR,

Normal ALT

Positive PCR,

Abnormal ALT

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset.
Accessed 01/18/03.MMWR 1998;47 (No. RR 19)

stop

STOP

stop

Medical Evaluation and

Management

for Chronic HCV Infection

 Assess for biochemical evidence of CLD
 Assess for severity of disease and possible

treatment, according to current practice

guidelines

 30-40% sustained response to antiviral

combination therapy (interferon alpha, ribavirin)

 Vaccinate against hepatitis A

 Counsel to reduce further harm to liver

 Limit or abstain from alcohol

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

HCV

Counseling

 Prevent transmission to others

 Direct exposure to blood
 Perinatal exposure
 Sexual exposure

 Refer to support group

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Preventing HCV Transmission

to Others

 Avoid direct exposure to blood

 Do not donate blood, body organs, other

tissue or semen

 Do not share items that might have blood

on them

 personal care (e.g., razor, toothbrush)
 home therapy (e.g., needles)

 Cover cuts and sores on the skin

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Persons Using Illegal Drugs

 Provide risk reduction counseling,

education

 Stop using and injecting
 Refer to substance abuse treatment program
 If continuing to inject

 Never reuse or share syringes, needles, or drug

preparation equipment

 Vaccinate against hepatitis B and hepatitis A
 Refer to community-based risk reduction programs

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Mother-to-Infant

Transmission of HCV

 Postexposure prophylaxis not available
 No need to avoid pregnancy or

breastfeeding

 Consider bottle feeding if nipples cracked/bleeding

 No need to determine mode of delivery

based on HCV infection status

 Test infants born to HCV-positive women

 Consider testing any children born since woman

became infected

 Evaluate infected children for CLD

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Sexual Transmission of HCV

 Persons with one long-term steady sex

partner

 Do not need to change their sexual practices
 Should discuss with their partner

 Risk (low but not absent) of sexual transmission
 Routine testing not recommended but counseling

and testing of partner should be individualized

 May provide couple with reassurance
 Some couples might decide to use barrier

precautions to lower limited risk further

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset.
Accessed 01/18/03.

Sexual Transmission of HCV

 Persons with high-risk sexual

behaviors

 At risk for sexually transmitted diseases,

e.g., HIV, HBV, gonorrhea, chlamydia, etc.

 Reduce risk

 Limit number of partners
 Use latex condoms

 Get vaccinated against hepatitis B
 MSMs also get vaccinated against hepatitis

A

Adapted from Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.

Mother-to-Infant Transmission of
HCV

 Postexposure prophylaxis not available
 No need to avoid pregnancy or breastfeeding

 Consider bottle feeding if nipples cracked/bleeding

 No need to determine mode of delivery

based on HCV infection status

 Test infants born to HCV-positive women

 Consider testing any children born since woman became

infected

 Evaluate infected children for CLD

Adapted from Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset.
Accessed 01/18/03.

Chronic HCV

Natural History

Features of Hepatitis C Virus

Infection

Incubation period

Average 6-7

weeks

Range 2-26

weeks

Acute Illness (Jaundice)

Mild (<20%)

Case Fatality Rate

Low

Chronic Infection

75%-85%

Chronic Hepatitis

70% (most asx)

Cirrhosis

10%-20%

Mortality from CLD

1% - 5%

Adapted from CDC Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed
01/18/03.

Disease Progression of HCV
*

*Adapted from Brown RS. Epidemiology and Natural History of Hepatitis C. Presented at an ACG Clinical Implications meeting April 6,
2000 in Dallas, TX.
1. NIH Consensus Development Conference Statement; March 24-26, 1997.
2. Davis GL et al. Gastroenterol Clin North Am. 1994;23:603-613.
3. Koretz RL et al. Ann Intern Med. 1993;119:110-115.
4. Takahashi M et al. Am J Gastroenterol. 1993;88:240-243.

Acute

HCV

Chronic HCV

Cirrhosis

Hepatic

Failure

Liver

Cancer

Liver Transplant

Candidates

~

85

%

1

20

-

50%

2

~ 20%

3

~ 20%

4

Chronic Hepatitis C Factors

Promoting Progression or

Severity

 Increased alcohol intake

 Age > 40 years at time of

infection

 HIV co-infection

 Other

 Male gender?

 Other co-infections (e.g., HBV)

Adapted from CDC Hepatitis Slide Kit
http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. Accessed 01/18/03.